REwired

It’s all in your head.

It’s the epicenter of who you are and what you are.

It’s your brain…and local physicians and researchers are

starting to solve some of the mysteries locked deep inside of it.

Written by Rosalind Fournier

Photography by Beau Gustafson

The Final Frontier

Ask them what draws them to the marvelously intriguing specimen known as the human brain, and they—the neurologists and neurosurgeons, clinicians and researchers—will tell you, almost to a person: It’s the final frontier.

“Think about when Harvey Cushing was taking out brain tumors back in the 1900s, says Dr. John C. Wellons III, a pediatric neurosurgeon at Children’s of Alabama hospital. “He’s the father of modern neurosurgery, and he was just happy to have someone survive. A few weeks ago I took out a tumor with an endoscope the size of a pencil with a little TV on the end of it, and we could look up at a screen and see everything we were doing inside the brain. We took the tumor out using microscopic instruments, and the girl went home on day two. That’s how far society and industry have brought us.

“This is a final frontier that combines science and the best technology available with a need to help people on the most primal level,” he says.

Birmingham doctors are immersed in some of the world’s most advanced brain laboratories, testing bold new theories and bringing their collective wealth of talent to bear in hopes of curing diseases of the brain, alleviating suffering and improving lives. The science is precise, because the brain leaves precious room for error. It moves quickly because the need and potential are so great.

Dr. Ray Watts, chairman of the Department of Neurology at the University of Alabama at Birmingham, asserts that these doctors are poised to develop new, life-saving treatments and potential cures for a range of confounding neurological conditions, from Parkinson’s disease to brain tumors and many in between. “This is a very exciting time in neuroscience,” he says. “I believe we are at the beginning of the Century of the Brain.”

In theory, the brain is a hostile environment for cancer. Confined by the skull and surrounded by brain tissue, it would appear any brain tumor would be landlocked, with no room for expansion.

The ugly truth, however, is that brain tumors find a way to make room for their own growth, explains Dr. Harald Sontheimer, director of the University of Alabama at Birmingham Civitan International Research Center and the UAB Center for Glial Biology in Medicine. In particular, he and his team study gliomas, aggressive malignant brain tumors that arise from tissue in the nervous system.

He explains that these gliomas release excessive amounts of glutamate in the brain. Normally, glutamate enables nerve cells to communicate with one another. “But when the tumor releases too much,” Sontheimer says, “the nerve cells begin firing uncontrollably, setting in motion seizures and exhausting themselves—ultimately dying and vacating room for the tumor to expand.”

Seeking a way to thwart this deadly process, Sontheimer’s laboratory considered that to produce glutamates, glial cells must first import the amino acid cystine into a neural pathway that Sontheimer calls a “revolving door.” They honed in on a drug called sulfasalazine that is commonly used to treat Chrone’s disease, an inflammatory disease of the intestines. It turns out this same drug has properties that can stop cystine uptake. In effect, it renders the cystine molecule “too large for that revolving door to revolve,” he says. “So it prevents the further release of glutamate, it prevents the seizures, and it prevents the tumor from growing.” In the best-case scenario, Sontheimer adds, a tumor may actually shrink as a result. So far, studies in mice as well as early anecdotal evidence from patients who have taken the drug have strongly upheld this theory.

Meanwhile, Sontheimer points to the importance of being able to link tumor growth and seizures by way of this hyper-production of glutamate. “In a large majority of cases, a seizure is what prompts patients to seek medical help,” Sontheimer says. “Very often in response to doing a brain scan one diagnoses a brain malignancy or brain tumor. It seems to be a relatively early presentation.

“If you have a patient with a glioma, typically it’s terrible news, because we don’t have much to offer in terms of treatment,” he continues. “But this offers hope, absolutely.”

Sontheimer says that he envisions controlled clinical studies taking place in the next year or two to collect more data on how seizures and tumors respond to the drug. In the meantime, physicians have already been contacting Sontheimer for dosing recommendations in order to offer patients this treatment option by prescribing sulfasalazine off-label.

“This is not something pie-in-the-sky, as in ‘Maybe years from now we’ll be able to treat people this way,’ he says. “It’s happening fast because there is a real need. These patients have no other hope.”

* * *

Dr. John (“Jay”) Wellons, a pediatric neurosurgeon at Children’s who is one of the HCRN’s principal investigators

“One of the scariest things as a parent to learn,” a parent wrote in a blog on Xconomy.com, “is that your child has a disease that has no cure.” That parent was Paul Gross, a former Microsoft executive whose son was born prematurely six years ago and developed hydrocephalus. “It was a big Greek word for a condition that had little medical research and its only treatment required brain surgery,” he says.

Gross set out to learn as much as he could about hydrocephalus, a condition that causes dangerous amounts of fluid to accumulate in the brain. Determined to find a way to help improve research in this area, he enlisted the help of fellow parents, physicians and philanthropists, and their efforts led to the Hydrocephalus Research Network (HCRN), a collaboration of pediatric neurosurgery centers working together to dramatically improve the lives of kids suffering from hydrocephalus through important, field-changing clinical research. Children’s of Alabama hospital became one of the founding four pediatric neurosurgery centers asked to join the network.

“The work we’re leading out of this center is specifically on what’s called post hemorrhagic hydrocephalus,” explains Dr. John (“Jay”) Wellons, a pediatric neurosurgeon at Children’s who is one of the HCRN’s principal investigators. Post-hemorrhagic hydrocephalus is one of the great risks of premature birth and very low birth weight, because these infants are more prone to brain hemorrhage and subsequent fluid buildup.

As part of the HCRN, neurosurgeons at Children’s are building a body of research that is invaluable to improving the consistency of treatment. By following the neurologic outcomes over time of patients tracked through the network, they are able to give hard numbers to theories about different treatment protocols.

“Believe it or not, there had not been a concerted effort before to try and do outcomes-driven research on hydrocephalus at a multi-center level,” Wellons says. “It’s hard to make statistical validation until you have the numbers to be able to say that treatment x is better than treatment y.”

The stakes are high: Among infants with post-hemorrhagic hydrocephalus, the eventual outcomes may be vastly different. “You can take the most severe post-hemorrhagic hydrocephalus patients and have two of them come into my clinic as six-year-olds,” Wellons says. “And I see one of them in one room, and it’s ‘Hey, Dr. Wellons! I got all A’s and a B on my report card.’ Then I take a very similar x-ray from six years ago and go into the next room, and this patient is wheelchair-bound and non-communicative.

“Do we know if the decisions we make early on get us from room number two to room number one? Or is it independent of things we do as surgeons? That’s what we’re working on. But if we can impact it a little bit, if we can make 15 percent of this population move from room two to room one, that would be fantastic.”

An early HCRN success was in bringing down the rate of infection in shunts, which are surgically inserted in hydrocephalus patients to divert fluid away from the brain. In fact, reducing infections associated with shunt surgery was the network’s very first initiative and achieved remarkable success. By standardizing protocol for the procedure, “We’ve been able to reduce it from around 8.5 percent to just around 5.5 percent using this quality-improvement methodology across all of the centers,” he says. A paper showing these results recently appeared in the Journal of Neurosurgery: Pediatrics, with Wellons and Dr. Jerry Oakes, chief of neurosurgery at Children’s, among the authors.

Wellons credits Oakes’ leadership with fostering a strong culture of research in the department, which is ranked no. 11 in the country by U.S. News and World Report for pediatric neurosurgery. He says that work they’re doing as part of the HCRN has pushed the department’s research agenda even further. “The effect among our pediatric neurosurgeons, PhDs, residents, nurses and other staff of this group is to say, ‘How can we apply the lessons we have learned in this hydrocephalus research to other pediatric neurosurgical diseases?’” he says. The University of Alabama now sends students from the School of Medicine and the School of Public Health to participate in outcomes-based research here.

Wellons says the HCRN is also a case study in the importance of philanthropy in medical research. It can even create a much-needed snowball effect at a time when all sources of funding are squeezed by the economy. “The philanthropic funding behind the HCRN has been crucial to our getting research done and papers published, so then we can go to the National Institutes of Health and demonstrate we’re a group that’s committed and finding time on top of their surgical case load to do this important work,” he says. This summer, he and other doctors involved in the study traveled to Bethesda, Md., to make a presentation to the National Institute of Neurological Disorders and Stroke about their study of shunting outcomes in post-hemorrhagic hydrocephalus.

Attention and money given to this disease translate to furthering the research. “And when more research is done,” Wellons says, “that means more questions are answered.”

* * *

When Dr. James H. Meador-Woodruff was a medical student in the early 1980s, schizophrenia was the number-one cause of hospitalization. “Not the number-one cause just in terms of psychiatry, but that includes all hospital beds, period. Think about that.” says Meador-Woodruff, who has been studying schizophrenia for 25 years and today is chair of psychiatry at UAB.

To put it bluntly, there was room for improvement in schizophrenia treatment, and Meador-Woodruff has been witness to the awe-inspiring progress that has been made. “We have deinstitutionalized an entire generation of people by discovering more effective drugs and better treatments,” he says, “Getting them out of the hospital, taking care of them in the community and seeing them have occupational and social success has been profound.”

Often, schizophrenia patients are admitted to the hospital during episodes of so-called “positive” and acute symptoms, such as hallucinations. Doctors can usually alleviate these symptoms quickly with antipsychotics. Dr. Robert McCullumsmith, director of UAB’s Adult Ambulatory Division, notes this has reduced hospital stays from months to mere days.

But what then?

Meador-Woodruff and McCullumsmith—who were colleagues at the University of Michigan, where Meador-Woodruff was vice chair of psychiatry and research professor of the Molecular and Behavioral Neuroscience Institute, before both men came to UAB in 2006—have now turned their attention to what they describe as the more intractable symptoms of schizophrenia, such as withdrawal and isolation, that can be so debilitating for patients.

“We’re able to treat the hallucinations and delusions pretty well, but the dramatic stuff is not the core of the illness,” Meador-Woodruff says. “The core is what we call the deficit state, or ‘negative symptoms’ like withdrawal, isolation and inability to manage that lead to occupational and social dysfunction. So our goal is actually to help these people maintain jobs and families, to have a higher quality of life.”

To that end, Meador-Woodruff and McCullumsmith recently received National Institutes of Health grants totaling $3.9 million to study causes of schizophrenia and new targets for treatment. As they describe it, the work has the potential to usher in another sea change for schizophrenia patients.

McCullumsmith explains that for decades, science has focused on the relationship between schizophrenia and dopamine. Dopamine is a naturally occurring neurotransmitter thought to cause psychotic illness when it is overactive. Existing drugs can block dopamine receptors and consequently block the positive symptoms of schizophrenia, but they do little to improve other symptoms, suggesting that “there’s a whole lot more to this story than just the dopamine hypothesis and drugs like Haldol and Thorazine,” he says. “We need drugs that can work in different parts of the brain than the drugs we have, using different mechanisms and possibly in combinations of lower doses, and help patients with schizophrenia not be as sick and function at a higher level.”

The area that has caught the doctors’ interest is in glutamate-transporter abnormalities. McCullumsmith says the focus on glutamate transporters came largely through the observation that taking the drug PCP, or angel dust, can cause symptoms that mimic schizophrenia. “We know that PCP binds to a very specific glutamate receptor,” he says. “When you block that receptor with a drug, all kinds of things go haywire.”

In schizophrenia, Meador-Woodruff explains, “We think what has happened is that the brain makes glutamate receptors normally, but they don’t get to where they’re supposed to be.

“I think it’s probably an overarching theme in a lot of psychiatric illnesses,” he adds. “So we’re looking at individual cells in order to understand, from the time a receptor was made, where did it go wrong?”

This involves studying actual human tissue from the brains of deceased schizophrenia patients—sort of the gold standard of brain research—and using cutting-edge techniques such as laser-capture micro-dissection. “We’ve developed a lot of really cool tools not seen outside of Star Trek,” Meador-Woodruff says. “The ability to take these brains, isolate individual cells and measure individual patterns of gene can revolutionize everything we think about mental illness.”

* * *

Psychiatrist and addiction specialist, Jerry Howell is a consultant for Bradford Heath Services and medical director for American Behavioral Benefits Managers.

“Don’t kid yourself,” psychiatrist Jerry Howell is fond of saying when he talks about addiction. “Drugs and alcohol work.”

He doesn’t mean it as a joke, or reverse psychology. He wants his audience to understand the vexing irony of addiction: Drugs and excessive alcohol cause immeasurable harm, but they sure do feel good going down.

“At the moment people decide to do a drug, they’re wanting something to happen,” Dr. Howell says. “Especially if they’re stressed out or feeling anxious, or they’re in physical or emotional pain, they take the drug, and guess what? It relieves it faster than having to deal with the problem itself.” By bypassing the need to deal with problems cognitively, drug use allows problem-solving skills to atrophy—particularly dangerous for a teenager, who is yet to fully develop those skills in the first place. At the same time, it wreaks havoc on the brain’s neurocircuitry responsible for sensing satisfaction and reward. “Natural” highs become much harder to come by, and the natural lows, when the brain is missing its fix, are lower than ever. “We used to think the brain wasn’t affected, but we know now that all levels of the brain are affected in addiction,” Howell says.

In effect, addiction is like a bully who hands you a crutch and then breaks your leg. How are you going to get around now?

Board-certified in both psychiatry and addiction, Howell’s expertise quietly touches lives across the region via several different medical entities. Currently psychiatric consultant for Bradford Heath Services and medical director for American Behavioral Benefits Managers, he is also former chief of psychiatry for Carraway Methodist Medical Center and for seven years did consult/liaison psychiatry for St. Vincent’s Hospital. He is a founder of the Alabama Society of Addiction. His services are also regularly sought out by the National Football League.

Early in his career, Howell was a dedicated—one might say workoholic—family doctor. He never drank or used drugs, but that changed during his first tour in Vietnam, the beginning of a treacherous path. “Was (Vietnam) the reason I was using? I don’t know, but I took that logic and ran with it,” he says. “As I look back on it, I was treating a lot of emotional pain more than anything else.”

Named Flight Surgeon of the Year for the United States Air Force in 1974, his success and identity as a well-respected doctor helped to fuel a sense of invincibility even as his problem spiraled into addiction. “For a lot of people, as long as they can work and do their job well, that’s the last thing to go in their lives,” he says. “There can be all kinds of devastation in your life, but as long as you can get up and go to work, that’s your identity.”

Howell entered at treatment in 1984. After he got out, he began helping other doctors with substance-abuse problems and quickly expanded to the population as a whole. He has learned and observed fundamental truths about addiction along with improvements in scientific understanding. More than anything he has learned a great deal from listening to addicts themselves. What he has seen has stripped him of any illusions that any one drug is safer than another.

“Because we have different personalities or different psychological makeups, people choose different things,” he says. “Their drug of choice, whatever it is, over and over again they tell me that’s what makes them feel ‘whole.’

“We have people who come into treatment for marijuana, and the other addicts say, ‘Oh, come on! Spare me!’ But I promise you marijuana can be just as hard as any drug to stop for that particular person. You ask him, have you ever had a problem with alcohol? No. Opiates? No. Cocaine? But he may be 50 years old and he’s been smoking pot since he was 15!”

Still, for all the talk of marijuana as a “gateway drug,” Howell points to nicotine as the ultimate “renaissance drug.”

“The most potent addiction is based on the principal of tobacco,” he says. “Most people start smoking in their adolesence. What happens in your adolescence? You’re stressed out, you’re anxious, you smoke a cigarette and it sort of calms you down. When you talk about effects on the brain, first of all, you’re starting with a pliable brain. Second, because it’s a vapor, it gets there in a hurry. The delivery system of the drug has a huge impact on the brain. When you suck vapor into your lungs, whether the smoke contains nicotine, cannabis, crack cocaine or whatever, it arrives at your brain eight seconds later. In the 1980s when people started smoking crack cocaine, that’s why so many became addicted so quickly—a lot of times even after the first use of the drug.”

Howell points to some of the pre-existing factors that contribute to different types of addiction. It has long been known that alcoholism has a strong genetic component, with a high pass-along rate from mother to daughter and father to son, for example. People who drink or take drugs to calm down may start and continue because of an underlying anxiety disorder. For these patients, the initial acute withdrawal is only the beginning trauma of coming off the drug. “This drug relieved your anxiety, and when you’re coming off if it, you suffer a deer-in-the-headlights type of anxiety,” he says. “It’s intense. The addict has promised himself a thousands times more than he promises anyone else he’s going to quit. But he goes into this terrible secondary withdrawal of despair, and that’s how a lot of people end up drifting back to opiates.”

In fact, Howell notes that the use of opiates has largely changed the face of addiction in recent years. “Lortab, Oxycontin, all of these morphine-derivative drugs, are rapidly becoming the number-one addiction problem in the country,” he says. “Often patients will take pain medicine as prescribed, and then one day they get stressed out and take more. They find that it relieves their emotional pain, as well.” In other cases, young people take prescription drugs recreationally only to develop a habit they can’t afford: “They start doing other things like lying and stealing. And then someone comes along and says, here’s something a lot cheapter. You can smoke it, snort it or shoot it. Kids start shooting heroin, and their lives just go downhill. But heroine is back with a bang.”

While people always seem to be finding new ways to get high—if you hear that people are abusing “bath salts,” for instance, don’t assume that means they’re soaking too long in the tub—the principals of getting sober are consistent. In essence, it’s hard work; treatment is only the beginning; and an addict must be committed to recovery for its own sake, rather than to satisfy mandates imposed by anyone or anything else. Still, Howell himself is a living, breathing example that people can overcome addiction.

“I promise everybody that the most demanding job in the world is being an alcoholic or an addict,” he says. “Because as you progress down the disease, you’re going to have to work at it all day, every day, overtime. I challenge anybody to give me a job that is as stressful as that.

“I can tell them, ‘You just quit the hardest job you’ll ever have.’”

* * *

A couple of years ago, the Parkinson Symposium of Alabama held a symposium on a therapy called deep brain stimulation, or DBS. It is basically a pacemaker for the brain that is implanted in the chest and emits a small electric current to help calm the part of the brain where Parkinson’s symptoms originate.

“We had four patients with DBS come in and sit onstage,” remembers Dr. David Standaert, professor of Neurology and director of the UAB Center for Neurodegeneration and Experimental Therapeutics (CNET). “You can turn the device on and off with a magnet, and one of our physicians went up and turned all four of them off. In the space of 10 or 15 seconds, each of them exhibited dramatic, different symptoms of Parkinson’s. And then he just went back and turned them on again. It was really amazing to see that kind of transformation.”

The Food and Drug Administration approved the DBS procedure in 1997, and some 700 operations have been done at UAB. “There are a lot of people walking around Birmingham with pacemakers in their chest and wires in their brain,” Standaert says. “It works.”

Since coming to UAB in 2006 after 14 years as a faculty member at Harvard Medical School, Standaert has essentially built the UAB Center for Neurodegeneration and Experimental Therapeutics from the ground up. Parkinson’s, along with Alzheimer’s, Huntingdon, Lou Gherig’s disease and other neurodegenerative disorders, are at the focus of the center, both through patient treatment and groundbreaking research.

Standaert is the director of CNET and was appointed chair of neurology at UAB in August. He personally sees patients in a weekly clinic and follows them through clinical trials in new Parkinson’s therapies. He serves on the Executive Scientific Advisory Board of the Michael J. Fox Foundation for Parkinson’s Research, which has funded many important studies at CNET.

Along with treating Parkinson’s symptoms, he and his lab are always looking toward what comes next. “We’re now talking about treatments that would alter the fundamental nature of the disease, or even prevent it,” Standaert says. “People might have been talking about it 10 years ago, but nobody had any idea what that might look like or how it might work. Today we have a lot more concrete ideas about how we might accomplish this. That’s been a big change.”

He points to the discovery of genes that have been shown to cause Parkinson’s. “This has been a huge clue,” he says. “Over the past decade five or possibly six different genes have been discovered which, in certain families, trigger the disease.” He says his lab is studying the roles that a protein called alpha-synuclein and mutations in the gene LRRK2 play in Parkinson’s.

“Now we have models we can test in a dish,” Standaert says, “and we can look for drugs that affect alpha-synuclein in LRRK2. So on the one hand, thinking concretely about having preventative or curative treatments is a big change, and then actually having systems where we can discover these is a big change, too.”

UAB has also recently become the only site in Alabama performing a test called the DaTscan for Parkinson’s, approved earlier this year by the FDA. “It’s a radioactive dye you inject into the blood, and when you do a scan it shows the depth of dopamine function in the brain,” Standaert says. Areas lacking in healthy dopamine neurons may indicate early brain degeneration.

Doctors have also found low-tech ways of identifying Parkinson’s patients before classic symptoms such as tremors, shakiness, stiffness and slow movement, and falling. “There is a whole group of things we now know go on before that,” Standaert says. “One is constipation, a very common early symptom, along with loss of smell and REM behavior disorder (in which people ‘act out’ their dreams while asleep). If you find those three things, in five years, more than half of them will have Parkinson’s disease.”

* * *

Dr. Robert C. Knowlton, associate professor of neurology at UAB and director of the UAB Seizure Monitoring Unit

Dr. Robert C. Knowlton initially came to the field of epilepsy by way of a detour. “I was interested in behavioral neurology,” says Knowlton, associate professor of neurology at UAB and director of the UAB Seizure Monitoring Unit. “Dementias, little weird strokes and very specific neurological abnormalities —‘The Man Who Who Mistook His Wife for A Hat’ Oliver Sacks-type stories.”

Sacks, himself a neurologist, published his famous collection of true—and truly bizarre—stories of neurological aberrations in 1985. While the symptoms Sacks described in his subjects captured Knowlton’s imagination, he realized what he really wanted was to be on the cutting edge of understanding how, why and where different symptoms originate inside the brain.

“When I got into neurology,” Knowlton says, “I saw pretty quickly that the best behavioral neurology is epilepsy.” He explains that epileptic seizures offer a front-line view into the link between specific areas in the brain and their functions. “In a large percentage of epilepsy patients the seizures come from one very focal point in the brain, and the best part of my job is to find out where it is. And when they experience seizures, if they remain relatively small, they can actually tell you what they are experiencing.” Charting the patient’s experience against the biological markers of the seizure, when that is possible, effectively creates a roadmap of the brain.

The primary goal, of course, is to address and resolve the point of origin and stop the seizures, specifically in patients whose seizures cannot be controlled by medications and may be candidates for surgery.

Where surgery is a viable option, this detailed roadmap is essentially not only to pointing the surgeon towards the problem but away from critical areas responsible for speech, movement and other major brain functions.

Studying seizures by definition involves casting a relatively wide net in terms of patients seen in the UAB-HSF MEG laboratory, which Knowlton directs and which uses some of the most technologically advanced equipment and methods available in the country. That’s because “any kind of abnormality in the brain can cause seizures,” he says. “It can be something you’re born with or acquired, trauma, strokes—anything you can think of.”

Tumors, either cancerous or benign, are major culprits in seizures and by definition more likely than other causes to mandate surgery. “Tumor doctors need epilepsy doctors to help them do precise mapping of normal function of the brain that needs to be avoided,” he says. “It’s a game of location, location, location.”

While patients can describe their experience of a seizure, finding physical neurological evidence to pinpoint that location is the trickiest part and most stimulating challenge of that game for Knowlton. In the ideal but rare instances when a patient can actually be observed in the hospital having a seizure, an injectable dye can clearly identify areas of related brain activity. However, most people do not experience seizures with anything like the kind of frequency or regularity that would make that possible, and epilepsy is elusive in terms of leaving residual evidence after a seizure has passed.

But Knowlton says new methods of brain imaging have transformed the field, and UAB has the only lab for Magnetoencephalography (MEG) in the Southeast and one of only a handful in the U.S. A technology that records electrical activity in the brain by way of magnetic fields,unlike has really enabled source imaging to move forward,” he says. “Unlike electrical signals themselves, magnetic fields are not attenuated by the bone or intervening tissues, which caused limitations we had to deal with for decades.”

It is also a technology, Knowlton argues, that owes a debt of gratitude to epilepsy.

“Epilepsy has really been at the forefront of pushing this technology because it has the most to gain in helping us localize where seizures come from,” he says. “It’s pushed those of us in epilepsy to become experts in imaging, and that’s a lot of fun.”

* * *

Autism is arguably is one of the most confounding neurological disorders of our time. It is estimated that one in 110 children today will be diagnosed with autism, which, depending whom you ask, either represents a dramatic spike or simply a reflection of greater awareness of the disorder (or maybe both). Autism is known to be a highly genetic disease, with as much as 90 percent of it caused by what you inherit from your parents, but undoubtedly there are other factors, some environmental, some statistical (otherwise known as luck of the draw), that determine who will be born autistic and who will not. And autism itself can express itself in any number of different ways, with different levels of severity.

But Dr. Andrew West, assistant professor of neurology and John A. and Ruth R. Jerenko Research Scholar at UAB, remains undeterred in looking for autism’s proverbial smoking gun, some “bottleneck” area through which all causative factors must pass before they can begin to cause developmental abnormalities. Targeting that area in the brain is key to stopping autism in its tracks. West likens it to some types of cancer research: “It’s known that you can have many alterations that feed to tumor genesis, but if you take out the key component needed for ultimate transition, then oftentimes the causes don’t really matter.”

West directs a lab in the Center for Neurodegeneration and Experimental Therapeutics focused on discovering the biochemical and genetic basis of neurodegenerative diseases. In a series of rooms filled with highly sophisticated technology, West and his team use DNA extracted from blood samples as well as brain tissue itself to study some of these suspected bottlenecks underlying the disease.

He also works with mouse models genetically engineered with a particular gene modification suspected to be present in a large fraction of people with autism.

He notes that the studies in mice have reinforced a promising theory. “They’ve shown us that when you know there are abnormalities in development that lead to psychiatric conditions, these are potentially reversible,” he says. Whereas in Parkinson’s the disease kills off the affected cells before they can be studied, “In autism the brain is right there. It is plastic enough to modify itself, and that’s exciting.”

* * *

Sandy Naramore, executive director Mitchell’s Place

Across town, Mitchell’s Place is a program and center established in 2005 to meet the specialized needs of children with autism and their families. What happens here reflects the tremendous potential that behavioral therapy has shown in helping autistic children reach their full potential.

Here “autism” and “autism spectrum” may be the common diagnosis, but executive director Sandy Naramore stresses that each child is different, with unique challenges and potential. “Nothing stands true for the whole population here,” she says. “Just like you and I are different, each child is totally independent from the next.”

Naramore says behavioral modification is based on close, one-on-one observation, patience, and repetition.

“We observe closely to see what is causing certain behaviors and find ways to correct it in a positive, not punitive way,” she says. “For instance, if it’s time to line-up and a child won’t stand in line, with our population, we don’t know—is he being defiant, or not processing? So we show him, this is what it means to line up. And we practice, because repetition is key.”

Dr. Sandra Cluett Redden, a developmental psychologist at Mitchell’s Place, says she was drawn to the field in part because her younger brother is on the autism spectrum. “We didn’t know as much about autism then, so we tried our best as a family to understand how this might impact him,” she says.

“What we focus on here is what we can do something about, in terms of how we can look at a child’s particular strengths and weaknesses and build them up from a behavioral standpoint, rather than focusing on the actual cause, but unfortunately at this point in time there’s not much we can do about that,” Redden notes. “We’re concentrating on where the child is and what we need to do to help them be more successful and gain more skills.”

Every day, Naramore is humbled by the progress she sees in the kids at Michell’s Place. “We’ve had kids who come in here and will not speak a word,” she says. “A couple of years later, they might run into my office, smile and say, ‘Hi, Sandy!’ It might not seem like much to you, but the difference is astounding from then to now. And they are so proud.”

Posted on Tuesday, November 1st, 2011.

One Response to “REwired”

Thank you for mentioning Mitchell’s Place in your magazine. As the grandfather of an autistic child who started attending Mitchell’s Place a year ago at the age of 2, and continues to attend to this day, I can testify to the accomplishments brought about by this outstanding institution. The facilities, therapist, teachers, and staff are absolutely the very best in my opinion. You will not find a more focused group of professionals anywhere. I have spent untold hours observing the day to day activities at the school and I know for a fact that these marvelous individuals spend every minute of every class day totally devoted to the children and their needs. Words can not fully express my appreciation for Mitchell’s Place and it’s staff.